BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
B-cell–driven relapse and anti-CD20 rescue therapy after Alemtuzumab in RRMS: case report and literature review
Provisionally accepted
Pietro Antonio Bruno1
Stefania Barone1Angelo Pascarella2Pier Luigi Lanza3Emanuele Tinelli4
Antonio Gambardella1Paola Valentino1*- 1Department of Medical and Surgical Sciences, Institute of Neurology, Magna Græcia University, Catanzaro, Italy
- 2Department of Medical and Surgical Sciences, Magna Græcia University of Catanzaro; Regional Epilepsy Centre, Great Metropolitan “Bianchi-Melacrino-Morelli” Hospital, Reggio Calabria., Reggio Calabria, Italy
- 3Biocontrol, Diagnostic Imaging Center, Cosenza, Italy
- 4Department of Medical and Surgical Sciences, Institute of Neuroradiology, Magna Graecia University,, Catanzaro, Italy
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Background: Alemtuzumab is an immune reconstitution therapy (IRT) approved for highly active relapsing– remitting multiple sclerosis (RRMS). Notably, the differential reconstitution of B and T cells after alemtuzumab may trigger paradoxical B–cell–mediated inflammation and secondary autoimmunity. Case Report: We describe the case of a 44-year-old woman with RRMS who experienced a severe, steroid-resistant relapse nine months after her second alemtuzumab cycle. Lymphocyte subtyping revealed disproportionate B-cell repopulation, suggesting a B-cell–mediated immunopathogenesis. Early ocrelizumab switch resulted in rapid clinical and radiological recovery and sustained stability. Literature Review: We conducted a narrative review of early and paradoxical disease reactivation after alemtuzumab, identifying common features: early onset, poor steroid response, large or tumefactive lesions, and marked B-cell hyperrepopulation. Anti-CD20 therapy often induced rapid remission. These findings may suggest a distinct B-cell–driven mechanism of inflammation. Prior exposure to fingolimod has been observed in several cases, but does not uniformly account for the observed phenotype. Conclusion: This case contributes to the growing evidence that a subset of patients may experience B-cell– driven inflammatory reactivation after alemtuzumab treatment. Lymphocyte subtyping should be performed, and a predominance of CD19+ B cells can guide a timely therapeutic switch to anti-CD20 therapy. Further studies are needed to define whether this represents a distinct post-IRT immunopathological entity.
Keywords: relapsing–remitting multiple sclerosis, alemtuzumab, Ocrelizumab, B cells, Steroid-resistant relapse, Immune reconstitution therapy, Secondary autoimmunity, neuroimmunology
Received: 22 Sep 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Bruno, Barone, Pascarella, Lanza, Tinelli, Gambardella and Valentino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Paola Valentino
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